Exercise ameliorates fine particulate matter-induced metabolic damage through the SIRT1/AMPKα/PGC1-α/NRF1 signaling pathway.

Air pollution, particularly fine particulate matter (PM2.5), poses a major threat to human health. Exercise has long been recognized as a beneficial way to maintain physical health. However, there is limited research on whether exercise can mitigate the damage caused by PM2.5 exposure. In this study, the mice were exercised on the IITC treadmill for 1 h per day, then exposed to concentrated PM2.5 for 8 h. After 2, 4 and 6-month exercise and PM2.5 exposure, the glucose tolerance and insulin tolerance were determined. Meanwhile, the corresponding indicators in epididymal white adipose tissue (eWAT), brown adipose tissue (BAT) and skeletal muscle were detected. The results indicated that PM2.5 exposure significantly increased insulin resistance (IR), while exercise effectively attenuated this response. The observations of muscle, BAT and eWAT by transmission electron microscopy (TEM) showed that PM2.5 significantly reduced the number of mitochondria in all of the three tissues mentioned above, and decreased the mitochondrial area in skeletal muscle and BAT. Exercise reversed the changes in mitochondrial area in all of the three tissues, but had no effect on the reduction of mitochondrial number in skeletal muscle. At 2 months, the expressions of Mfn2, Mfn1, OPA1, Drp1 and Fis1 in eWAT of the PM mice showed no significant changes when compared with the corresponding FA mice. However, at 4 months and 6 months, the expression levels of these genes in PM mice were higher than those in the FA mice in skeletal muscle. Exercise intervention significantly reduced the upregulation of these genes induced by PM exposure. The study indicated that PM2.5 may impact mitochondrial biogenesis and dynamics by inhibiting the SIRT1/AMPKα/PGC1-α/NRF1 pathway, which further lead to IR, glucose and lipid disorders. However, exercise might alleviate the damages caused by PM2.5 exposure.

Modulation of the gut microbiota and lipidomic profiles by black chokeberry (Aronia melanocarpa L.) polyphenols via the glycerophospholipid metabolism signaling pathway.

Black chokeberry (Aronia melanocarpa L.) is rich in polyphenols with various physiological and pharmacological activities. However, the relationship between the modulation effect of black chokeberry polyphenols on obesity and the alteration of lipid metabolism is not clearly understood. This study aimed to investigate the beneficial effects of the black chokeberry polyphenols (BCPs) treatment on the structure of gut microbiota, lipid metabolism, and associated mechanisms in high-fat diet (HFD)-induced obese rats. Here, we found that a high-fat diet promoted body weight gain and lipid accumulation in rats, while oral BCPs supplementation reduced body weight, liver, and white adipose tissue weight and alleviated dyslipidemia and hepatic steatosis in HFD-induced obese rats. In addition, BCPs supplementation prevented gut microbiota dysbiosis by increasing the relative abundance of Bacteroides, Prevotella, Romboutsia, and Akkermansia and decreasing the relative abundance of Desulfovibrio and Clostridium. Furthermore, 64 lipids were identified as potential lipid biomarkers through lipidomics analysis after BCPs supplementation, especially PE (16:0/22:6), PE (18:0/22:6), PC (20:3/19:0), LysoPE (24:0), LysoPE (24:1), and LysoPC (20:0). Moreover, our studies provided new evidence that composition of gut microbiota was closely related to the alteration of lipid profiles after BCPs supplementation. Additionally, BCPs treatment could ameliorate the disorder of lipid metabolism by regulating the mRNA and protein expression of genes related to the glycerophospholipid metabolism signaling pathway in HFD-induced obese rats. The mRNA and protein expression of PPARα, CPT1α, EPT1, and LCAT were significantly altered after BCPs treatment. In conclusion, the results of this study indicated that BCPs treatment alleviated HFD-induced obesity by modulating the composition and function of gut microbiota and improving the lipid metabolism disorder via the glycerophospholipid metabolism signaling pathway.

The prevalence, relative risk factors and MTHFR C677T genotype of H type hypertension of the elderly hypertensives in Shanghai, China: a cross-section study : Prevalence of H type hypertension.

BACKGROUND: H type hypertension is defined as homocysteine (Hcy) ≥ 10 µmol/L in combination with primary hypertension. Studies demonstrated that the existence of hyperhomocysteine (HHcy) in hypertensive exacerbates the poor outcome of cardiocerebral incidents. This study was to investigate the current epidemic situation of H type hypertension and determine the risk factors in order to find intervention targets for H type hypertensives. METHODS: We conducted a cross-sectional study using cluster sampling design in Shanghai, China from July 2019 and April 2020. 23,652 patients with primary hypertension were enrolled in this study. Their medical information was recorded, and the level of Hcy concentrations and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms were detected. RESULTS: In total, 22,731 of 23,652 patients were recorded. The mean age was 68.9 ± 8.6 y and 43% were men. 80.0% of the enrolled patients had H type hypertension. The frequency of allele T was 40.9%, and the proportions of the CC, CT, and TT genotypes were 36.1%, 46.0%, and 17.9%, respectively. Compared with the TT genotype, the plasma Hcy concentration levels were lower in patients with the CC/CT genotype (18.96 ± 13.48 µmol/L vs. 13.62 ± 5.20/14.28 ± 5.36, F = 75.04, p < 0.01). The risk for H type hypertension was higher in elderly people. Men had ~ 5.55-fold odds of H type hypertension compared with women. Patients with CT genotype and TT genotype had ~ 1.36- and ~ 2.76-fold odds of H type hypertension compared with those with CC genotype, respectively. Smoking and diabetes were not significantly associated with H type hypertension. CONCLUSIONS: The prevalence of H type hypertension in patients with primary hypertension was 80.0%, which was higher than the 75% found in prior report in China. Age, gender, and MTHFR C677T polymorphisms rather than smoking and diabetes were independently associated with H type hypertension.

Health related quality of life and its impacts by chronic diseases in urban community population, Shanghai, China in 2015.

This survey aimed to describe the health-related quality of life (HRQoL) and to explore the relationship between chronic diseases and HRQoL among urban residents in Shanghai, China. A cross-sectional study of 9 426 adults was conducted in Xuhui District of Shanghai, China in 2015. The EuroQol five-dimension three-level (EQ-5D-3 L) was used to measure HRQoL. The average age of subjects was 55.6 ± 17.4 years and 53% were female. Their mean values of utility and visual analogue scale (VAS) were 0.974 ± 0.099 and 80.00 ± 12.36, respectively, which were above the Chinese norm values. Women had lower scores compared with men. The utility value decreased with age, which accelerated after the age of 55 years. Chronic conditions including diabetes, tumor, cardiovascular disease, and respiratory disease, were significantly related to HRQoL, and the reported proportions of problems in the five dimensions increased with the number of chronic diseases (p < 0.05). Chronic diseases except for respiratory disease had a negative effect on HRQoL utility value and VAS score after the adjustment for covariates (p < 0.05). Chronic diseases had a negative impact on both EQ-5D-3 L utility and VAS scores, although the health-related quality of life for the study was above the national average.

Ruthenium-Catalyzed Enantioselective C-H Functionalization: A Practical Access to Optically Active Indoline Derivatives.

Ru(II)-catalyzed enantioselective C-H activation/hydroarylation has been developed for the first time, allowing for highly enantioselective synthesis of indoline derivatives via catalytic C-H activation. Commercially available Ru(II) arene complexes and chiral α-methylamines were employed as highly enantioselective catalysts. Based on a sterically rigidified chiral transient directing group, multisubstituted indolines were produced in up to 92% yield with 96% ee. Further transformation of the resulting 4-formylindoline enables access to an optically active tricyclic compound that is of potential biological and pharmaceutical interest.

Glucose impairs angiogenesis and promotes ventricular remodelling following myocardial infarction via upregulation of microRNA-17.

Hyperglycaemia is known to impair angiogenesis, which may contribute to the poor prognosis of diabetic patients following myocardial infarction (MI). miR-17 has been reported to be involved in the proliferation, migration, and angiogenesis of a variety of vascular endothelial cells. However, how miR-17 regulates angiogenesis under hyperglycaemic conditions has not been reported. Thus, the aim of this study was to investigate the role of miR-17 in the impairment of angiogenesis induced by high glucose. In vitro, human umbilical vein endothelial cells (HUVECs) transfected with miR-17 mimics or inhibitors were incubated with normal-glucose or high-glucose (HG) medium. In vivo, miR-17 or negative control antagomirs were administered by tail vein injection in an MI model of streptozotocin (STZ)-induced diabetic mice. MiR-17 was upregulated, while VEGFA was downregulated in MI mice with diabetes and in HUVECs exposed to HG. The luciferase reporter gene assay confirmed that VEGFA is a target gene of miR-17. Moreover, inhibition of miR-17 prevented HG-induced VEGFA downregulation and impaired the capacity for migration and tube formation in HUVECs. Administration of miR-17 antagomirs significantly improved LV function and reduced infarct size in diabetic post-MI mice. Furthermore, the effects of diabetes-induced decreases in angiogenesis and VEGFA expression were abrogated by miR-17 antagomirs treatment in diabetic infarcted myocardium. These findings suggest that inhibition of miR-17 prevents HG-induced impairment of angiogenesis and improves cardiac function after MI by targeting VEGFA in diabetic mice.

The value of multidisciplinary team in syncope clinic for the effective diagnosis of complex syncope.

BACKGROUND: Syncope is a perplexing challenge that often receives thorough evaluation, yet the diagnosis remains unclear. Usually, the emergency department is the first point at which patients present with syncope. However, diverse medical factors, including low diagnostic rates and inconsistent management by doctors, add to healthcare costs and delay diagnosis for syncope patients. METHODS: Patients who had been to the emergency department at least once but were not given a clear diagnosis of syncope were recruited into our study at the time they visited syncope clinic staffed by a multidisciplinary team. Complete medical histories and clinical examinations were conducted by both experienced cardiologists and neurologists. If patients were not given a conclusive diagnosis at the syncope clinic on the basis of outpatient examinations, they were admitted for further evaluation. RESULTS: A total of 209 consecutive patients claiming "syncope" visited the syncope clinic, yet only 167 patients were formally diagnosed with syncope. For these 167 patients, the mean age was 55.93 ± 17.40 years old, and 41.3% were male. The proportions of cardiac syncope, reflex syncope, orthostatic hypotension (OH), and syncope of uncertain etiology were 19.8%, 64.1%, 7.8%, and 8.4%, respectively. The diagnostic rate was 91.6%, and the hospitalization rate was 23.4%. Patients with reflex syncope and OH were younger than patients with cardiac syncope. Cardiac syncope tends to occur more frequently in males, while reflex syncope is more likely in females. CONCLUSIONS: The cooperation of professional cardiologists and neurologists will play an important role in improving diagnostic rates, lowering admission rates, and reducing medical costs.

Synthesis, bioactivity and mode of action of 5A 5B 6C tricyclic spirolactones as novel antiviral lead compounds.

BACKGROUND: Plant viral diseases cause tremendous decreases in yield and quality. Natural polycyclic compounds such as those containing carbocycles are often very important lead compounds for drug and pesticide development. Tricyclic spiranoid lactones with 5A 5B 6C -ring fusion topologies possess various bioactivities. In this study, 33 new 5A 5B 6C tricyclic spirolactones were rationally designed, synthesized, characterized and evaluated for antiviral activities. RESULT: These compounds showed no apparent toxicity against Italian honeybees up to 2.73 µg bee-1 . Spirolactones 14, 16, 19, 23 and 28 at a concentration of 100 µg mL-1 inactivated 90% of tobacco mosaic virus (TMV) infection, making these compounds much more potent than the positive controls. Significantly, compound 19 displayed the best inactivation activity causing inhibition of up to 98%. CONCLUSION: The results of the bioassays and QSAR studies indicated that the carbon-containing cyclic moiety was the antiviral pharmacophore, and derivative 19, which showed the best inactivation activity, could emerge as a potential antiviral agent against TMV. In vitro capsid protein (CP) assembly and TMV assembly inhibition determinations indicated that these compounds induced crosslinking in the TMV and prevented its uncoating, which was a putative new mode of action for TMV inactivation. © 2018 Society of Chemical Industry.

Changes in smoking prevalence after the enforcement of smoking control regulations in urban Shanghai, China: Findings from two cross-sectional surveys.

INTRODUCTION: The Smoking Control Regulation in Public Places (hereafter, the 'regulations') has been implemented in Shanghai since 2010. This study explores the changes in smoking prevalence and its influencing factors among urban Shanghai residents. METHODS: Two rounds of household investigations (the Health Status and Health Service Utilization Survey) were carried out using a multistage probability proportionate-to-size sampling method in an urbanized district in 2010 and 2015. Descriptive and logistic regression analyses were applied to the statistics. RESULTS: From 2010 to 2015, the standardized current smoking rate fell from 24.8% to 19.1% (38.3% to 32.0% among men, and 1.9% to 1.4% among women). Meanwhile, the standardized smoking cessation rate increased from 18.1% to 23.3%. Smoking prevalence in respondents aged 45 to 59 years was still higher than that of other age groups. Changes in smoking prevalence and cessation rates were more obvious in respondents aged 30-44 and over 75 years. Sex, age, education, marital status, and alcohol use were influencing factors of current smoking, while sex, age and alcohol use were influencing factors of smoking cessation. CONCLUSIONS: The implementation of smoking control regulations may be beneficial for reducing smoking and increasing smoking cessation, especially among middle-aged and older men. Nevertheless, tobacco control in urban Shanghai still faces huge challenges. Therefore, more targeted and comprehensive measures should be taken.

Acute effects of fine particles on cardiovascular system: differences between the spontaneously hypertensive rats and wistar kyoto rats.

The study is to explore the potential mechanisms linking fine particles and cardiovascular toxicity. Spontaneous hypertensive rats (SHR) and age-matched wistar kyoto (WKY) rats were exposed by intratracheal instillation to fine particles with the doses of 0.0, 1.6, 8.0 and 40.0mg/kg b.w., respectively. The exposure was conducted once a day, for three continuous days. Twenty-four hours after the last exposure, the rats were killed and the levels of high sensitive C-reactive proteins (hsCRPs), nitrous oxide (NO), D-dimer and endothelin-1 (ET-1) were measured in blood. Reverse transcriptase polymerase chain reaction (RT-PCR) assay assessed the expression of interleukin-1 beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1), ET-1, Bax and Bcl-2 in left ventricle of rats. Meanwhile, cardiac histological lesions were assessed. The expression transforming growth factor-beta 1 (TGF-beta(1)) in left ventricle was measured by immunohistochemical staining. The results showed that the levels of hsCRP, D-dimer, ET-1 and the expression of IL-1beta, ICAM-1, ET-1, Bax and TGF-beta(1) increased in a dose-dependent manner, but NO and Bcl-2 decreased. Cardiac histology demonstrated exacerbated cardiac lesions in SHR when compared to WKY rats. Meanwhile, at the same dose exposed, the levels of hsCRP, d-dimer, ET-1 and the expression of IL-1beta, ICAM-1, ET-1, Bax and TGF-beta(1) were higher in SHR than those in WKY rats. The results indicated that ambient fine particles which entered into lungs could influence the cardiovascular system. When exposed to fine particles, SHR exhibited more severe cardiovascular injury in comparison to WKY rats. The results indicated that the inflammation, endothelial dysfunction, coagulation disorders and imbalance of apoptosis/anti-apoptosis might be the mechanisms of cardiovascular injury induced by fine particles. Different response between SHR and WKY rats after exposed to fine particles indicated that SHR was more susceptible than WKY rats to acute cardiac impairments from fine particle exposure.

[Acute effects of fine particle on cardiovascular system of rats].

OBJECTIVE: To observe the effects of fine particle on cardiovascular system of rats and compare fine particle toxicity on rats suffered from different condition and find the possible toxicological mechanism of fine particle. METHODS: Fine particle were collected using Thermo Anderson G-2.5 apparatus in Shanghai. Twenty-four spontaneous hypertension rats (SHR) and age-matched twenty-four WKY rats were used as subjects in order to study the effects of fine particle on cardiovascular system. The animals were divided into four groups and submitted to the instillation of saline and different dose fine particle. Twenty-four hours after instillation, direct measurements of arterial blood pressure and observation of electrocardiogram were obtained by catheterization of the carotid, and collected blood serum for measuring enzymes. RESULTS: With the increase of the concentration of fine particle, blood pressures and heart rates of WKY rats and SHR significantly increased. In every treatment groups, the blood pressures and heart rates were higher than those of control groups. At the same time, not only in WKY rats but also in SHR, the levels of lactate dehydrogenase (LDH) and MB isoenzyme of creatine kinase (CK-MB) were increased with the concentration of fine particle, and the levels of two kinds of enzymes in exposure groups were more higher than those of control groups. Furthermore, the levels of two kinds of enzymes of SHR groups at the doses of different treatment were more than those of WKY rats. CONCLUSION: The results showed that fine particle could be cardiovascular system toxicity for WKY rats and SHR, and SHR seemed more susceptible to fine particle than those of WKY rats.